Electrical stimulation with thermal treatment or thermal monitoring

ABSTRACT

Embodiments herein relate to medical devices and methods for using the same to treat cancerous tumors within a bodily tissue. A medical device system is included having an electric field generating circuit configured to generate one or more electric fields and a control circuit in communication with the electric field generating circuit. The control circuit configured to control delivery of the one or more electric fields from the electric field generating circuit. The system can include two or more electrodes to deliver the electric fields to a site of a cancerous tumor within a patient and a temperature sensor to measure the temperature of tissue at the site of the cancerous tumor. The control circuit can cause the electric field generating circuit to generate one or more electric fields at frequencies selected from a range of between 10 kHz to 1 MHz. Other embodiments are also included herein.

This application is a continuation application of U.S. patentapplication Ser. No. 16/855,448, filed Apr. 22, 2020, which claims thebenefit of U.S. Provisional Application No. 62/837,416, filed Apr. 23,2019, the contents of which are herein incorporated by reference intheir entirety.

FIELD

Embodiments herein relate to medical devices and methods for using thesame to treat cancerous tumors within a bodily tissue.

BACKGROUND

According to the American Cancer Society, cancer accounts for nearly 25%of the deaths that occur in the United States each year. The currentstandard of care for cancerous tumors can include first-line therapiessuch as surgery, radiation therapy, and chemotherapy. Additionalsecond-line therapies can include radioactive seeding, cryotherapy,hormone or biologics therapy, ablation, and the like. Combinations offirst-line therapies and second-line therapies can also be a benefit topatients if one particular therapy on its own is not effective.

Cancerous tumors can form if one normal cell in any part of the bodymutates and then begins to grow and multiply too much and too quickly.Cancerous tumors can be a result of a genetic mutation to the cellularDNA or RNA that arises during cell division, an external stimulus suchas ionizing or non-ionizing radiation, exposure to a carcinogen, or aresult of a hereditary gene mutation. Regardless of the etiology, manycancerous tumors are the result of unchecked rapid cellular division.

SUMMARY

In a first aspect, a medical device system is included having anelectric field generating circuit configured to generate one or moreelectric fields and a control circuit in communication with the electricfield generating circuit. The control circuit can be configured tocontrol delivery of the one or more electric fields from the electricfield generating circuit. The system can include two or more electrodesto deliver the electric fields to a site of a cancerous tumor within apatient and a temperature sensor to measure the temperature of tissue atthe site of the cancerous tumor, the temperature sensor in electroniccommunication with the control circuit. The control circuit can causethe electric field generating circuit to generate one or more electricfields at frequencies selected from a range of between 10 kHz to 1 MHz.

In a second aspect, in addition to one or more of the preceding orfollowing aspects, or in the alternative to some aspects, the system caninclude a first lead providing electrical communication between thecontrol circuit and at least one electrode; wherein the temperaturesensor is disposed on the first lead.

In a third aspect, in addition to one or more of the preceding orfollowing aspects, or in the alternative to some aspects, the first leadcan include at least one of a transcutaneous lead and a fully implantedlead.

In a fourth aspect, in addition to one or more of the preceding orfollowing aspects, or in the alternative to some aspects, at least twoelectrodes are configured to be implanted.

In a fifth aspect, in addition to one or more of the preceding orfollowing aspects, or in the alternative to some aspects, the electricfields are delivered across at least one vector defined by an electrodepair.

In a sixth aspect, in addition to one or more of the preceding orfollowing aspects, or in the alternative to some aspects, thetemperature sensor is positioned between the electrode pair.

In a seventh aspect, in addition to one or more of the preceding orfollowing aspects, or in the alternative to some aspects, thetemperature sensor is adapted to be inserted into the cancerous tumor.

In an eighth aspect, in addition to one or more of the preceding orfollowing aspects, or in the alternative to some aspects, the electricfields are delivered across at least two vectors, wherein a first vectoris defined by a first pair of electrodes and a second vector is definedby a second pair of electrodes.

In a ninth aspect, in addition to one or more of the preceding orfollowing aspects, or in the alternative to some aspects, wherein theelectric fields along the at least two vectors are spatially and/ordirectionally separated from one another.

In a tenth aspect, in addition to one or more of the preceding orfollowing aspects, or in the alternative to some aspects, the system caninclude at least two electric field generating circuits, wherein a firstelectric field generating circuit is implanted and a second electricfield generating circuit is external.

In an eleventh aspect, in addition to one or more of the preceding orfollowing aspects, or in the alternative to some aspects, the system canfurther include an implanted housing, the implanted housing defining aninterior volume into which the electric field generating circuit and thecontrol circuit are disposed.

In a twelfth aspect, in addition to one or more of the preceding orfollowing aspects, or in the alternative to some aspects, thetemperature sensor is selected from the group consisting of athermistor, a resistance thermometer, a thermocouple, and asemi-conductor based sensor.

In a thirteenth aspect, a medical device system is included having anelectric field generating circuit configured to generate one or moreelectric fields and a control circuit in communication with the electricfield generating circuit, the control circuit configured to controldelivery of the one or more electric fields from the electric fieldgenerating circuit. The system can include two or more electrodesforming at least one electrode pair to deliver the electric fields to asite of a cancerous tumor within a patient. The control circuit cancause the electric field generating circuit to generate one or moreelectric fields at frequencies selected from a range of between 10 kHzto 1 MHz. The control circuit can calculate a power output of theelectric field and estimate a temperature of tissue within the electricfield based on the power output and a distance between the electrodes ofthe electrode pair.

In a fourteenth aspect, in addition to one or more of the preceding orfollowing aspects, or in the alternative to some aspects, the medicaldevice system is configured to receive data regarding the distancebetween the electrodes of the electrode pair.

In a fifteenth aspect, in addition to one or more of the preceding orfollowing aspects, or in the alternative to some aspects, the medicaldevice system is configured to estimate the distance between theelectrodes of the electrode pair based on impedance data.

In a sixteenth aspect, a medical device system is included having anelectric field generating circuit configured to generate one or moreelectric fields and a control circuit in communication with the electricfield generating circuit, the control circuit configured to controldelivery of the one or more electric fields from the electric fieldgenerating circuit. The system can further include two or moreelectrodes forming at least one electrode pair to deliver the electricfields to a site of a cancerous tumor within a patient and wherein thecontrol circuit causes the electric field generating circuit to generateone or more electric fields at frequencies selected from a range ofbetween 10 kHz to 1 MHz. The control circuit can estimate a temperatureof tissue within the electric field based on an impedance measurement.

In a seventeenth aspect, in addition to one or more of the preceding orfollowing aspects, or in the alternative to some aspects, the controlcircuit estimates a temperature of tissue within the electric fieldbased on an impedance measurement and a distance between the electrodesof the electrode pair.

In an eighteenth aspect, in addition to one or more of the preceding orfollowing aspects, or in the alternative to some aspects, the medicaldevice system is configured to receive data regarding the distancebetween the electrodes of the electrode pair.

In a nineteenth aspect, in addition to one or more of the preceding orfollowing aspects, or in the alternative to some aspects, the controlcircuit estimates changes in temperature of tissue within the electricfield based on changes in measured impedance.

In a twentieth aspect, in addition to one or more of the preceding orfollowing aspects, or in the alternative to some aspects, the system canfurther include a heating element, wherein the control circuit causesthe heating element to generate heat.

This summary is an overview of some of the teachings of the presentapplication and is not intended to be an exclusive or exhaustivetreatment of the present subject matter. Further details are found inthe detailed description and appended claims. Other aspects will beapparent to persons skilled in the art upon reading and understandingthe following detailed description and viewing the drawings that form apart thereof, each of which is not to be taken in a limiting sense. Thescope herein is defined by the appended claims and their legalequivalents.

BRIEF DESCRIPTION OF THE FIGURES

Aspects may be more completely understood in connection with thefollowing figures (FIGS.), in which:

FIG. 1 is a schematic view of a medical system in accordance withvarious embodiments herein.

FIG. 2 is a schematic view of a medical system in accordance withvarious embodiments herein.

FIG. 3 is a plot of an exemplary therapy parameter in accordance withvarious embodiments herein.

FIG. 4 is a plot of an exemplary therapy parameter in accordance withvarious embodiments herein.

FIG. 5 is a schematic view of a medical device in accordance withvarious embodiments herein.

FIG. 6 is a schematic view of a medical device in accordance withvarious embodiments herein.

FIG. 7 is a schematic view of a medical device in accordance withvarious embodiments herein.

FIG. 8 is a schematic view of a medical device in accordance withvarious embodiments herein.

FIG. 9 is a schematic view of a medical device in accordance withvarious embodiments herein.

FIG. 10 is a schematic view of a medical device in accordance withvarious embodiments herein.

FIG. 11 is a schematic cross-sectional view of a medical device inaccordance with various embodiments herein.

FIG. 12 is a schematic diagram of components of a medical device inaccordance with various embodiments herein.

FIG. 13 is a flowchart depicting a method in accordance with variousembodiments herein.

While embodiments are susceptible to various modifications andalternative forms, specifics thereof have been shown by way of exampleand drawings, and will be described in detail. It should be understood,however, that the scope herein is not limited to the particular aspectsdescribed. On the contrary, the intention is to cover modifications,equivalents, and alternatives falling within the spirit and scopeherein.

DETAILED DESCRIPTION

As referenced above, many cancerous tumors can result from uncheckedrapid cellular division. Some traditional first-line therapies to treatcancerous tumors can include surgery, radiation therapy, andchemotherapy. However, many first-line therapies have undesirableconcomitant side effects, such as fatigue, hair loss, immunosuppression,and long surgical recovery times, to name a few.

While not intending to be bound by theory, it is believed that electricfields can disrupt mitosis within a cancerous tumor, such as byinterfering with the dipole alignment of key proteins involved incellular division; tubulin and septin in particular. The polymerizationof tubulin proteins that form microtubule spindle fibers can bedisrupted, thus preventing the formation of spindle fibers required forchromosome separation. This can halt cellular division at the metaphasestage of mitosis. In some instances, an electric field can haltpolymerization of already growing spindle fibers, leading to incompletespindles and unequal chromosome separation during anaphase, should thecell survive that long. In each case, halting microtubule spindleformation and unequal chromosome separation during anaphase caused byincomplete polymerization of microtubules, can result in apoptosis(i.e., programmed cell death). It is also believed that alternatingelectric fields can lead to increased electric field density near thecleavage furrow of the dividing cells during telophase. An increasedelectric field density in the region of the cleavage furrow can resultin dielectrophoresis of charged macromolecules, such as proteins andnucleic acids, toward the high electric field density at the furrow. Theunequal concentration of key macromolecules required for cellulardivision at the site of the cleavage furrow can disrupt the finalseparation of the sister cells during telophase and eventually lead toapoptosis.

Temperature can be in important parameter to measure during theadministration of an electrical field. In some cases, it may bedesirable to limit and/or prevent thermal destruction of tissues. Assuch, the temperature of tissue can be monitored (directly orindirectly) in order to prevent the temperature from rising to a levelwhere the thermal destruction of tissue may occur. However, in someembodiments, a degree of heating in combination with the application ofan electrical field may be therapeutic. Thus, in some embodiments, itmay be desirable to apply heat to tissue.

As such, various embodiments disclosed herein include a medical devicesystem that can generate an electric field for treatment of cancer thatcan include, or can control, at least one electrode, and/or at least onetemperature sensor or at least one heating element. In variousembodiments, an electric field can be generated, and heat can beapplied, such as via a heating element, to treat a tumor. In variousembodiments, a temperature sensor can be used to monitor the temperatureof tissue near or around an electric field or a heating element, such asto observe changes to tissue during heating or electric fieldgeneration. In various embodiments, the medical device can be configuredto turn off or stop the therapy if the temperature of the tissue exceeda threshold.

Referring now to FIG. 1 , a schematic view is shown of a medical device100 in accordance with various embodiments herein. The medical device100 can be implanted entirely within the body of a patient 101 at ornear the site of a cancerous tumor 110 located within a bodily tissue.Various implant sites can be used including areas such as in the limbs,the upper torso, the abdominal area, the head, and the like.

Referring now to FIG. 2 , another schematic view is shown of a medicaldevice 200 in accordance with various embodiments herein. The medicaldevice 200 can be external but can be connected to a component, such asleads, that are at least partially implanted within the body of apatient 101. In some embodiments, the medical device 200 can bepartially implanted and partially external to the body of a patient. Insome embodiments, the medical device 200 can include a transcutaneousconnection between components disposed internal to the body and externalto the body. In various embodiments, the medical device system describedherein can include an implanted medical device 100 and an externalmedical device 200. In other embodiments, the medical device systemdescribed herein can include a partially implanted medical device.

An implanted portion of a medical device system, such as an implantedmedical device 100 or portion thereof, can wirelessly communicatepatient identification data, diagnostic information, electric fielddata, physiological parameters, software updates, and the like with afully or partially external portion of a medical device 200 over awireless connection. Implanted medical device 100 can also wirelesslycommunicate with an external device configured to wirelessly charge themedical device utilizing inductance, radio frequency, and acousticenergy transfer techniques, and the like.

In some embodiments, a portion of a medical device or system can beentirely implanted, and a portion of the medical device can be entirelyexternal. For example, in some embodiments, one or more electrodes orleads can be entirely implanted within the body, whereas the portion ofthe medical device that generates an electric field, such as an electricfield generator, can be entirely external to the body. It will beappreciated that in some embodiments described herein, the electricfield generators described can include many of the same components asand can be configured to perform many of the same functions as a pulsegenerator. In embodiments where a portion of a medical device isentirely implanted, and a portion of the medical device is entirelyexternal, the portion of the medical device that is entirely externalcan communicate wirelessly with the portion of the medical device thatis entirely internal. However, in other embodiments a wired connectioncan be used for the implanted portion to communication with the externalportion.

The implanted medical device 100 and/or the medical device 200 caninclude a housing 102 and a header 104 coupled to the housing 102.Various materials can be used to form the housing 102. In someembodiments, the housing 102 can be formed of a material such as ametal, ceramic, polymer, composite, or the like. In some embodiments,the housing 102, or one or more portions thereof, can be formed oftitanium. The header 104 can be formed of various materials, but in someembodiments the header 104 can be formed of a translucent polymer suchas an epoxy material. In some embodiments the header 104 can be hollow.In other embodiments the header 104 can be filled with components and/orstructural materials such as epoxy or another material such that it isnon-hollow.

In some embodiments where a portion of the medical device 100 or 200 ispartially external, the header 104 and housing 102 can be surrounded bya protective casing made of durable polymeric material. In otherembodiments, where a portion of a device is partially external, theheader 104 and housing 102 can be surrounded by a protective casing madeof one or more of a polymeric material, metallic material, and/or glassmaterial.

The header 104 can be coupled to one or more leads 106. The header 104can serve to provide fixation of the proximal end of one or more leads106 and electrically couple the one or more leads 106 to one or morecomponents within the housing 102. The one or more leads 106 can includeone or more electrodes 108 disposed along the length of the electricalleads 106. In some embodiments, electrodes 108 can include electricfield generating electrodes and in other embodiments electrodes 108 caninclude electric field sensing electrodes. In some embodiments, leads106 can include both electric field generating and electric fieldsensing electrodes. In other embodiments, leads 106 can include anynumber of electrodes that are both electric field sensing and electricfield generating. The leads 106 can include one or more conductorstherein, such as metal wires, to provide electrical communicationbetween the electrodes and a proximal end (or plug) of the lead. Thewires can exist as single strands or fibers or can be multifibrillarsuch as a cable. The leads 106 can include a shaft, typically formed ofa polymeric material or another non-conductive material, within whichthe conductors therein can pass. The proximal end of the leads 106 canbe inserted into the header 104, thereby providing electricalcommunication between the electrodes 108 and the components inside thehousing 102. It will be appreciated that while many embodiments ofmedical devices herein are designed to function with leads, leadlessmedical devices that generate electrical fields are also contemplatedherein.

In various embodiments, the electrodes 108 can be positioned around oradjacent to a tumor 110, such as a cancerous tumor. The tumor 110 can bepositioned within an electric field generated by the electrodes 108.

The electric fields generated by the implanted medical device 100 and/orthe medical device 200 can vary. In some embodiments, the implantedmedical device 100 and/or the medical device 200 can generate one ormore electric fields at frequencies selected from a range of between 10kHz to 1 MHz.

In some embodiments, an electric field can be applied to the site of acancerous tumor at a specific frequency or constant frequency range.However, in some embodiments, an electric field can be applied to thesite of a cancerous tumor by sweeping through a range of frequencies. Asone example, referring now to FIG. 3 , exemplary plot 312 shows analternating electric field, delivered by the electrodes 108, where thefrequency increases over time. Similarly, FIG. 4 shows the change infrequency as a function of time in exemplary plot 414 during aprogrammed therapy parameter. In some embodiments, a frequency sweep caninclude sweeping from a minimum frequency up to a maximum frequency. Insome embodiments, a frequency sweep can include sweeping from a maximumfrequency down to a minimum frequency. In other embodiments, sweepingfrom a minimum frequency up to a maximum frequency and sweeping from themaximum frequency down to the minimum frequency can be repeated as manytimes as desired throughout the duration of the delivery of the electricfield from the electric field generating circuit.

As therapy progresses during a frequency sweep, it may be desired toalternate between frequency ranges so that as the cells within apopulation change in size and number in response to therapy, more cellscan be targeted. For example, in some embodiments, a frequency sweep caninclude alternating between a first frequency sweep covering a range ofabout 100 kHz to 300 kHz and a second frequency sweep covering a rangeabout 200 kHz to 500 kHz. It will be appreciated that sweeping through afirst and second frequency range as described can be performedindefinitely throughout the course of the therapy. In some embodiments,the second frequency sweep (range) can be at higher frequencies than thefirst frequency sweep (range). In some embodiments, the first frequencysweep (range) can be at higher frequencies than the second frequencysweep (range).

Frequency ranges for the first and second frequency ranges can be anyrange including specific frequencies recited above or below, providedthat the lower end of each range is a value less than the upper end ofeach range. At times, it may be beneficial to have some amount ofoverlap between the frequency range of the first and second frequencysweep.

Medical Devices and Systems

In reference now to FIG. 5 , a schematic view of a medical device 500 isshown in accordance with various embodiments herein. In variousembodiments, the medical device 500 can include at least one electricfield generating circuit configured to generate one or more electricfields. The electric field generating circuit can be disposed within thehousing 102. The medical device 500 can further include controlcircuitry that can be in communication with the electric fieldgenerating circuit. The control circuitry can be configured to controldelivery of the one or more electric fields from the electric fieldgenerating circuit. In various embodiments, the control circuitry causesthe electric field generating circuit to generate one or more electricfields at frequencies selected from a range of between 10 kHz to 1 MHz.In various embodiments, the medical device 500 can include an implantedhousing 102. The implanted housing 102 can define an interior volumeinto which the electric field generating circuit and the first controlcircuit are disposed.

In some embodiments, the medical device 500 can include one or moreleads 106, such as two leads 106 (although embodiments with three, four,five, six or more leads are also directly contemplated herein). In someembodiments, at least one of the leads 106 can be fully implanted orfully beneath the patient's skin 516, such as shown in FIG. 5 . In someembodiments, a plurality of leads 106 are fully implanted, such as twoleads 106, three leads 106, four leads 106, five leads 106, or six leads106. In some embodiments, at least two electrodes 108 are implanted anddisposed on a fully implanted lead 106. In various embodiments, the lead106 can be a transcutaneous lead that extends across the patient's skin516, such as shown in FIG. 8 .

In various embodiments, the medical device 500 can include two or moreelectrodes 108. The electrodes 108 can be configured to deliver theelectric fields to the site of a cancerous tumor 110. In variousembodiments, a lead 106 can provide electrical communication between thecontrol circuitry and at least one electrode 108. In variousembodiments, an electric field can be delivered across at least onevector 520 defined by a pair of electrodes 108 formed by two or moreelectrodes 108. In some embodiments, the electric fields can bedelivered across at least two vectors. In some embodiments, a firstvector can be defined by a first pair of electrodes and a second vectorcan be defined by a second pair of electrodes.

Temperature Sensor

In some embodiments, the medical device can include at least onetemperature sensor 518. The temperature sensor 518 can be configured tomeasure the temperature of tissue at the site of the tumor 110, such asto monitor temperature changes that could be a result of electric fieldgeneration or changes that could be a result of heating with a heatingelement. The temperature sensor 518 can be in electronic communicationwith the control circuitry. In some embodiments, the medical device caninclude at least one temperature sensor 519 which is disposed in tissuewhich is not within the region being treated, such as within healthytissue. The temperature sensor 519, which is remote from the treatmentregion, can be used along with temperature sensors 518 to determinechanges in temperature that are a result of the therapy.

Many different types of sensors can be used as a temperature sensorherein. In some embodiments, the temperature sensor 518 can be selectedfrom the group consisting of a thermistor, a resistance thermometer, athermocouple, a semi-conductor based sensor, a bimetallic device, athermometer, a change-of-state sensor, an optical temperature sensor(such as an infrared sensor), and the like.

In some embodiments, the temperature sensor 518 can be disposed on alead 106. In some embodiments, a plurality of temperature sensors 518can be disposed on a single lead 106. In some embodiments, at least onetemperature sensor 518 is disposed on each of the leads 106. In someembodiments with multiple leads 106, at least two of the leads 106 canhave a temperature sensor 518 disposed on the lead 106.

In some embodiments herein, a temperature sensor can be chronicallyimplanted. In some embodiments, a temperature sensor can be implantedfor greater than 1, 2, 4, 8, 12, 24, 52 or more weeks, or an amountfalling within a range between any of the foregoing. However, in someembodiments, a temperature sensor can be transitorily implanted. In someembodiments, a temperature sensor can be implanted for less than 2 days,1 day, 12 hours, 4 hours, 2 hours, or 1 hour, or an amount fallingwithin a range between any of the foregoing. In some embodiments, atemperature sensor 518 can be removable, such that it can be removedafter confirmation that the medical device is delivering therapy in asafe or expected manner. In various embodiments, during implanting ofthe electrodes 108, a removeable temperature sensor can be implanted.The removeable temperature sensor can be configured to measure thetemperature of tissue near one or more electrodes, such as duringimplanting the of the electrodes. The removeable temperature sensor canbe mounted on a transitorily inserted lead, introducer sheath, guidewire, delivery catheter, other type of catheter, or other type ofsurgical or implant instrument.

In some embodiments, a patient can undergo a thermal scan, such as aftera medical device has been implanted. The thermal scan can be conductedby an external device or component. The thermal scan can determinetemperatures of tissues in the patient's body, such as tissues near theelectrodes. The thermal scan can allow for a less intrusive manner tomonitor the temperature of various tissues within the patient's body,such as during therapy by a medical device.

It will be appreciated that a thermal scan can be performed in variousways. For example, a thermal scan can be performed using infraredthermography (IRT), an infrared thermometer, thermal imaging, thermalvideo, indium antimonide (InSb) devices, mercury cadmium telluride (MCT)devices, and the like.

Temperature Estimation Based on Power Output

In some embodiments, the control circuitry can be configured tocalculate the power output of the electric field. The control circuitcan also be configured to estimate a temperature of tissue within theelectric field, such as based on the power output and the distancebetween the electrodes 108 of the electrode pair. Power (in Watts) isrelated to current and resistance/impedance as follows P_(avg)=I²_(rms)*R. 1 watt is equivalent to 1 joule/second. Heat transferred canbe determined as q=mC_(p)ΔT or ΔT=q/mCp, wherein q is energy inkilojoules, m is the mass, Cp is the specific heat capacity of thetissue, and ΔT is the change in temperature. Thus, ΔT can beapproximated as I² _(rms)*R/mCp. In some embodiments, the distance (D)between electrodes can be used as a proxy for mass. Thus, in someembodiments, ΔT can be approximated as I² _(rms)*R/DCp. The specificheat capacity of the tissue can be about 3.6 to 3.9 kJ kg⁻¹ K⁻¹.

In some embodiments, the control circuit can be configured to estimate apower output based on a change in temperature. Specifically, theequations above can reconfigure to solve for P_(avg) based on ΔT.

In some embodiments, the medical device 500 can be configured to receivedata regarding the distance between two electrodes 108 in an electrodepair, such as to estimate the temperature of the tissue within theelectric field. In some embodiments, the medical device 500 can receivedata regarding the distance between two electrodes from a user. As anexample, a user can enter the distance during a programming phase. Insome embodiments, a user, such as a physician, can use an imagingdevice, such as a fluoroscope or ultrasound imaging device, to determinethe distance between two electrodes 108. The data can then be enteredinto the medical device 500. In further embodiments, the medical device500 can be configured to estimate the distance between the electrodes108 of an electrode pair, such as based on impedance data between thetwo electrodes 108.

Temperature as a Function of Impedance

In some embodiments, the control circuitry can be configured to estimatethe temperature of tissue within the electric field, such as based on animpedance measurement. In some embodiments, the control circuitry can beconfigured to estimate the temperature of tissue within the electricfield, such as based on an impedance measurement and the distancebetween the electrodes 108 of the electrode pair. The medical device 500can be configured to receive data regarding the distance between theelectrodes 108 of the electrode pair. In further embodiments, thecontrol circuitry can be configured to estimate changes in temperatureof tissue within the electric field, such as based on changes inmeasured impedance.

In various embodiments, the impedance of tissue can change as thetemperature of the tissue changes. These changes in impedance can becharacterized and compared to known data for the therapy device.Afterwards, the impedance measurements can be correlated to atemperature estimate of the tissue.

In reference now to FIG. 6 , a schematic view of a medical device 500 isshown in accordance with various embodiments herein. In someembodiments, the medical device 500 can include a temperature sensor 518positioned between a pair of electrodes 108. In some embodiments, thetemperature sensor 518 can be adapted to be inserted into the tumor 110.

In some embodiments, the lead 106 which the temperature sensor 518 isdisposed on does not include an electrode. In some embodiments, the lead106 can include a plurality of temperature sensors 518.

Heating Therapy

In some embodiments, the therapy delivered by the medical device 500 caninclude generating an electric field and generating heat at the tumor110. FIG. 7 is a schematic view of a medical device 500 in accordancewith various embodiments herein. In some embodiments, the medical device500 can include a heating element 722. The heating element 722 can beconfigured to generate heat. In various embodiments, the heating element722 can generate heat simultaneously with the electrodes generating anelectric field.

The heating element 722 can generate heat and cause tissue to be heatedthrough various means. In some embodiments, the heating element 722 mayoperate to heat tissue through conduction. For example, the heatingelement 722 may itself heat up through joule heating (also known asOhmic or resistive heating) which can be performed by passing anelectric current through a component with electrical resistance. Forexample, a nichrome (nickel/chromium 80/20) wire, ribbon, or stripeither directly exposed or embedded within another material can be usedas a heating element 722 and as it is heated it can heat the surroundingtissue through thermal conduction. Various other materials can also beused as a heating element. In some embodiments, the heating element 722may emit electromagnetic radiation that is then absorbed by thesurrounding tissue causing it to heat up. For example, the heatingelement 722 can include an infrared light emitter which generateselectromagnetic radiation that can be absorbed the surrounding tissueraising its temperature, which can serve as an example of radiantheating. In some embodiments, the heating element 722 can provide heatto tissue both through conduction and radiation.

In some embodiments, the control circuitry causes the heating element722 to generate heat. In some embodiments, the control circuitryestimates the temperature of tissue within the electric field based onan impedance measurement. In some embodiments, the control circuitryestimates the temperature of the tissue within the electric field basedon a power measurement.

In various embodiments, one or more heating elements 722 can be disposedon a lead 106. In some embodiments, a lead 106 which includes a heatingelement 722 does not include an electrode 108.

In some embodiments, a lead 106 can include at least one heating element722 and at least one electrode 108, such as shown in FIG. 8 . FIG. 8shows a schematic view of a medical device 500 in accordance withvarious embodiments herein. The medical device 500 can include a housing102 (which can be an external housing in this example) and one or moreleads 106.

The medical device 500 can include one or more transcutaneous leads 106,such as a lead 106 that passes through or across the patient's skin 516.In various embodiments, at least two electrodes 108 are implanted anddisposed on a transcutaneous lead 106. In various embodiments, at leasttwo electrodes 108 are implanted and disposed on transcutaneous leads106, such as at least one electrode 108 on two different transcutaneousleads 106.

External Power Source

In some cases, device operations herein may consume a significant amountof electrical power. By way of example, joule heating may consume asignificant amount of electrical power. The power capacity of fullyimplanted components may be somewhat limited (e.g., there are finitelimits to the total power capacity provided by implanted batteries). Assuch, in some embodiments, the system may be configured to deliver powerto an internal (implanted) component from an external power source.

FIG. 9 show a schematic view of a medical device 500 in accordance withvarious embodiments herein. The medical device 500 can include animplanted housing 902 and one or more fully implanted leads 906. Theimplanted leads 906 can include electrodes 108. The medical device 500can include an external housing 924. In some embodiments, an externalpower supply can be disposed within the external housing 924. In variousembodiments, the implanted housing 902 can be in wireless communicationwith the external housing 924, such as exchange data or informationregarding therapy delivery.

In some embodiments, control circuitry can be disposed in one of theimplanted housing 902 or the external housing 924. In some embodiments,control circuitry can be disposed at least partially in the implantedhousing 902 and the external housing 924.

In some embodiments, a transcutaneous lead 106 can include a wirelesspower transfer connection 940. The wireless power transfer connection940 can be established transcutaneously between the external housing924, such as a power supply within an external housing 924, and animplanted lead 106. In some embodiments, the medical device 500 caninclude an inductive power transfer link, including paired internal 942and external 944 inductors to transfer power form outside of the body toan implanted component of the system. The inductive power transfer linkcan allow for a transfer of power from an external power supply to aninternal component, which in turn can cause an electrical field to begenerated or heat to be generated without puncturing the skin 516 orotherwise requiring a maintained opening or tunnel through the patient'sskin 516.

In various embodiments, the fully implanted leads 906 can includeelectrodes 108 and can be free of heating elements 722, and thetranscutaneous lead 106 can include one or more heating elements 722. Insome embodiments, the external housing 924 can include a power source,such as to power the heating elements 722.

In reference now to FIG. 10 a schematic view of a medical device 500 isshown in accordance with various embodiments herein. In someembodiments, the electric fields can be delivered across at least twovectors 520, 920. The first vector 520 can be defined by a first pair ofelectrodes 108, and the second vector 920 can be defined by a secondpair of electrodes 108. In various embodiments, the first vector 520 andthe second vector 920 can be substantially orthogonal to one another.

In some embodiments, the medical device 500 can include at least twoelectric field generating circuits. In various embodiments, a firstelectric field generating circuit can be implanted, such as within thehousing 902, and a second electric field generating circuit can beexternal, such as within the housing 924.

Referring now to FIG. 11 , a schematic cross-sectional view of medicaldevice 1100 is shown in accordance with various embodiments herein. Thehousing 102 can define an interior volume 1102 that can be hollow andthat in some embodiments is hermetically sealed off from the area 1104outside of medical device 1100. In other embodiments the housing 102 canbe filled with components and/or structural materials such that it isnon-hollow. The medical device 1100 can include control circuitry 1106,which can include various components 1108, 1110, 1112, 1114, 1116, and1118 disposed within housing 102. In some embodiments, these componentscan be integrated and in other embodiments these components can beseparate. In yet other embodiments, there can be a combination of bothintegrated and separate components. The medical device 1100 can alsoinclude an antenna 1124, to allow for unidirectional or bidirectionalwireless data communication, such as with an external device or anexternal power supply. In some embodiments, the components of medicaldevice 1100 can include an inductive energy receiver coil (not shown)communicatively coupled or attached thereto to facilitate transcutaneousrecharging of the medical device via recharging circuitry.

The various components 1108, 1110, 1112, 1114, 1116, and 1118 of controlcircuitry 1106 can include, but are not limited to, a microprocessor,memory circuit (such as random access memory (RAM) and/or read onlymemory (ROM)), recorder circuitry, controller circuit, a telemetrycircuit, a power supply circuit (such as a battery), a timing circuit,and an application specific integrated circuit (ASIC), a rechargingcircuit, amongst others. Control circuitry 1106 can be in communicationwith an electric field generating circuit 1120 that can be configured togenerate electric current to create one or more fields. The electricfield generating circuit 1120 can be integrated with the controlcircuitry 1106 or can be a separate component from control circuitry1106. Control circuitry 1106 can be configured to control delivery ofelectric current from the electric field generating circuit 1120. Insome embodiments, the electric field generating circuit 1120 can bepresent in a portion of the medical device that is external to the body.

In some embodiments, the control circuitry 1106 can be configured todirect the electric field generating circuit 1120 to deliver an electricfield via leads 106 to the site of a cancerous tumor located within abodily tissue. In other embodiments, the control circuitry 1106 can beconfigured to direct the electric field generating circuit 1120 todeliver an electric field via the housing 102 of medical device 1100 tothe site of a cancerous tumor located within a bodily tissue. In otherembodiments, the control circuitry 1106 can be configured to direct theelectric field generating circuit 1120 to deliver an electric fieldbetween leads 106 and the housing 102 of medical device 1100. In someembodiments, one or more leads 106 can be in electrical communicationwith the electric field generating circuit 1120.

In some embodiments, various components within medical device 1100 caninclude an electric field sensing circuit 1122 configured to generate asignal corresponding to sensed electric fields. Electric field sensingcircuit 1122 can be integrated with control circuitry 1106 or it can beseparate from control circuitry 1106.

Sensing electrodes can be disposed on or adjacent to the housing of themedical device, on one or more leads connected to the housing, on aseparate device implanted near or in the tumor, or any combination ofthese locations. In some embodiments, the electric field sensing circuit1122 can include a first sensing electrode 1132 and a second sensingelectrode 1134. In other embodiments, the housing 102 itself can serveas a sensing electrode for the electric field sensing circuit 1122. Theelectrodes 1132 and 1134 can be in communication with the electric fieldsensing circuit 1122. The electric field sensing circuit 1122 canmeasure the electrical potential difference (voltage) between the firstelectrode 1132 and the second electrode 1134. In some embodiments, theelectric field sensing circuit 1122 can measure the electrical potentialdifference (voltage) between the first electrode 1132 or secondelectrode 1134, and an electrode disposed along the length of one ormore leads 106. In some embodiments, the electric field sensing circuitcan be configured to measure sensed electric fields and to recordelectric field strength in V/cm.

It will be appreciated that the electric field sensing circuit 1122 canadditionally measure an electrical potential difference between thefirst electrode 1132 or the second electrode 1134 and the housing 102itself. In other embodiments, the medical device can include a thirdelectrode 1136, which can be an electric field sensing electrode or anelectric field generating electrode. In some embodiments, one or moresensing electrodes can be disposed along lead 106 and can serve asadditional locations for sensing an electric field. Many combinationscan be imagined for measuring electrical potential difference betweenelectrodes disposed along the length of one or more leads 106 and thehousing 102 in accordance with the embodiments herein.

In some embodiments, the one or more leads 106 can be in electricalcommunication with the electric field generating circuit 1120. The oneor more leads 106 can include one or more electrodes 108, as shown inFIGS. 1 and 2 . In some embodiments, various electrical conductors, suchas electrical conductors 1126 and 1128, can pass from the header 104through a feed-through structure 1130 and into the interior volume 1102of medical device 1100. As such, the electrical conductors 1126 and 1128can serve to provide electrical communication between the one or moreleads 106 and control circuitry 1106 disposed within the interior volume1102 of the housing 102.

In some embodiments, recorder circuitry can be configured to record thedata produced by the electric field sensing circuit 1122 and record timestamps regarding the same. In some embodiments, the control circuitry1106 can be hardwired to execute various functions, while in otherembodiments the control circuitry 1106 can be directed to implementinstructions executing on a microprocessor or other external computationdevice. A telemetry circuit can also be provided for communicating withexternal computation devices such as a programmer, a home-based unit,and/or a mobile unit (e.g. a cellular phone, personal computer, smartphone, tablet computer, and the like).

Elements of various embodiments of the medical devices described hereinare shown in FIG. 12 . However, it will be appreciated that someembodiments can include additional elements beyond those shown in FIG.12 . In addition, some embodiments may lack some elements shown in FIG.12 . The medical devices as embodied herein can gather informationthrough one or more sensing channels and can output information throughone or more field generating channels. A microprocessor 1202 cancommunicate with a memory 1204 via a bidirectional data bus. The memory1204 can include read only memory (ROM) or random-access memory (RAM)for program storage and RAM for data storage. The microprocessor 1202can also be connected to a telemetry interface 1218 for communicatingwith external devices such as a programmer, a home-based unit and/or amobile unit (e.g. a cellular phone, personal computer, smart phone,tablet computer, and the like) or directly to the cloud or anothercommunication network as facilitated by a cellular or other datacommunication network. The medical device can include a power supplycircuit 1220. In some embodiments, the medical device can include aninductive energy receiver coil interface (not shown) communicativelycoupled or attached thereto to facilitate transcutaneous recharging ofthe medical device.

The medical device can include one or more electric field sensingelectrodes 1208 and one or more electric field sensor channel interfaces1206 that can communicate with a port of microprocessor 1202. Themedical device can also include one or more electric field generatingcircuits 1222, one or more electric field generating electrodes 1212,and one or more electric field generating channel interfaces 1210 thatcan communicate with a port of microprocessor 1202. The medical devicecan also include one or more temperature sensors 1216 and one or moretemperature sensor channel interfaces 1214 that can communicate with aport of microprocessor 1202. The channel interfaces 1206, 1210, and 1214can include various components such as analog-to-digital converters fordigitizing signal inputs, sensing amplifiers, registers which can bewritten to by the control circuitry in order to adjust the gain andthreshold values for the sensing amplifiers, source drivers, modulators,demodulators, multiplexers, and the like.

Although the temperature sensors 1216 are shown as part of a medicaldevice in FIG. 12 , it is realized that in some embodiments one or moreof the temperature sensors could be physically separate from the medicaldevice. In various embodiments, one or more of the temperature sensorscan be within another implanted medical device communicatively coupledto a medical device via telemetry interface 1218. In yet otherembodiments, one or more of the temperature sensors can be external tothe body and coupled to a medical device via telemetry interface 1218.

Methods

Many different methods are contemplated herein, including, but notlimited to, methods of making, methods of using, and the like. Aspectsof system/device operation described elsewhere herein can be performedas operations of one or more methods in accordance with variousembodiments herein.

In an embodiment, a method of treating a cancerous tumor is included.The method can include implanting at least two electrodes inside a bodyof a patient with the cancerous tumor, implanting a temperature sensorinside the body of the patent, generating an electrical field between atleast one pair of electrodes, the electric field having frequencieswithin a range of between 10 kHz to 1 MHz, and sensing the temperaturewith the temperature sensor.

FIG. 13 shows a flowchart depicting a method 1300 in accordance withvarious embodiments herein. The method 1300 can be a method for treatinga cancerous tumor. The method 1300 can include implanting at least twoelectrodes inside a body of a patient with the cancerous tumor, step1330. The method 1300 can further include implanting a temperaturesensor inside the body of the patent, step 1332, such as near or withinthe cancerous tumor. The method 1300 can also include generating anelectrical field between at least one pair of electrodes, step 1334. Invarious embodiments, the electric field can have frequencies within arange of between 10 kHz to 1 MHz.

In some embodiments, the method 1300 can include sensing the temperaturewith the temperature sensor, step 1336, such as the temperature of thetissue near the tumor or the temperature of the tumor. In someembodiments, the method 1300 can include estimating the temperature oftissue within the electric field, such as based on the power output andthe distance between the electrodes. In some embodiments, the method1300 can include estimating the distance between electrodes of anelectrode pair, such as based on impedance data.

Electrical Stimulation Parameters

In various embodiments, systems or device herein (or components thereof,such as control circuitry) can be configured to direct an electric fieldgenerating circuit to deliver an electric field using one or morefrequencies selected from a range of between 10 kHz to 1 MHz. In someembodiments, the control circuitry can be configured to direct theelectric field generating circuit to deliver an electric field at one ormore frequencies selected from a range of between 100 kHz to 500 kHz. Insome embodiments, the control circuitry can be configured to direct theelectric field generating circuit to deliver an electric field at one ormore frequencies selected from a range of between 100 kHz to 300 kHz. Insome embodiments, the control circuitry can be configured to direct theelectric field generating circuit to periodically deliver an electricfield using one or more frequencies greater than 1 MHz.

In some embodiments, the electric field can be effective in disruptingcellular mitosis in cancerous cells. The electric field can be deliveredto the site of a cancerous tumor along more than one vector. In someexamples, the electric field can be delivered along at least one vector,including at least one of the lead electrodes. In some embodiments, atleast two vectors with spatial diversity between the two vectors can beused. The vectors can be spatially and/or directionally separated (e.g.,the vectors can be disposed at an angle with respect to one another) byat least about 10, 20, 30, 40, 50, 60, 70, 80 or 90 degrees.

A desired electric field strength can be achieved by delivering anelectric current between two electrodes. The specific current andvoltage at which the electric field is delivered can vary and can beadjusted to achieve the desired electric field strength at the site ofthe tissue to be treated. In some embodiments, the control circuitry canbe configured to direct the electric field generating circuit to deliveran electric field using currents ranging from 1 mAmp to 1000 mAmp to thesite of a cancerous tumor. In some embodiments, the control circuitrycan be configured to direct the electric field generating circuit todeliver an electric field using currents ranging from 20 mAmp to 500mAmp to the site of a cancerous tumor. In some embodiments, the controlcircuitry can be configured to direct the electric field generatingcircuit to deliver an electric field using currents ranging from 30 mAmpto 300 mAmp to the site of a cancerous tumor.

In some embodiments, the control circuitry can be configured to directthe electric field generating circuit to deliver an electric field usingcurrents including 1 mAmp, 2 mAmp, 3 mAmp, 4 mAmp, 5 mAmp, 6 mAmp, 7mAmp, 8 mAmp, 9 mAmp, 10 mAmp, 15 mAmp, 20 mAmp, 25 mAmp, 30 mAmp, 35mAmp, 40 mAmp, 45 mAmp, 50 mAmp, 60 mAmp, 70 mAmp, 80 mAmp, 90 mAmp, 100mAmp, 125 mAmp, 150 mAmp, 175 mAmp, 200 mAmp, 225 mAmp, 250 mAmp, 275mAmp, 300 mAmp, 325 mAmp, 350 mAmp, 375 mAmp, 400 mAmp, 425 mAmp, 450mAmp, 475 mAmp, 500 mAmp, 525 mAmp, 550 mAmp, 575 mAmp, 600 mAmp, 625mAmp, 650 mAmp, 675 mAmp, 700 mAmp, 725 mAmp, 750 mAmp, 775 mAmp, 800mAmp, 825 mAmp, 850 mAmp, 875 mAmp, 900 mAmp, 925 mAmp, 950 mAmp, 975mAmp, or 1000 mAmp. It will be appreciated that the control circuitrycan be configured to direct the electric field generating circuit todeliver an electric field at a current falling within a range, whereinany of the forgoing currents can serve as the lower or upper bound ofthe range, provided that the lower bound of the range is a value lessthan the upper bound of the range.

In some embodiments, the control circuitry can be configured to directthe electric field generating circuit to deliver an electric field usingvoltages ranging from 1 V_(rms) to 50 V_(rms) to the site of a canceroustumor. In some embodiments, the control circuitry can be configured todirect the electric field generating circuit to deliver an electricfield using voltages ranging from 5 V_(rms) to 30 V_(rms) to the site ofa cancerous tumor. In some embodiments, the control circuitry can beconfigured to direct the electric field generating circuit to deliver anelectric field using voltages ranging from 10 V_(rms) to 20 V_(rms) tothe site of a cancerous tumor.

In some embodiments, the control circuitry can be configured to directthe electric field generating circuit to deliver an electric field usingone or more voltages including 1 V_(rms), 2 V_(rms), 3 V_(rms), 4V_(rms), 5 V_(rms), 6 V_(rms), 7 V_(rms), 8 V_(rms), 9 V_(rms), 10V_(rms), 15 V_(rms), 20 V_(rms), 25 V_(rms), 30 V_(rms), 35 V_(rms), 40V_(rms), 45 V_(rms), or 50 V_(rms). It will be appreciated that thecontrol circuitry can be configured to direct the electric fieldgenerating circuit to deliver an electric field using a voltage fallingwithin a range, wherein any of the forgoing voltages can serve as thelower or upper bound of the range, provided that the lower bound of therange is a value less than the upper bound of the range.

In some embodiments, the control circuitry can be configured to directthe electric field generating circuit to deliver and electric fieldusing one or more frequencies including 10 kHz, 20 kHz, 30 kHz, 40 kHz,50 kHz, 60 kHz, 70 kHz, 80 kHz, 90 kHz, 100 kHz, 125 kHz, 150 kHz, 175kHz, 200 kHz, 225 kHz, 250 kHz, 275 kHz, 300 kHz, 325 kHz, 350 kHz, 375kHz, 400 kHz, 425 kHz, 450 kHz, 475 kHz, 500 kHz, 525 kHz, 550 kHz, 575kHz, 600 kHz, 625 kHz, 650 kHz, 675 kHz, 700 kHz, 725 kHz, 750 kHz, 775kHz, 800 kHz, 825 kHz, 850 kHz, 875 kHz, 900 kHz, 925 kHz, 950 kHz, 975kHz, 1 MHz. It will be appreciated that the electric field generatingcircuit can deliver an electric field using a frequency falling within arange, wherein any of the foregoing frequencies can serve as the upperor lower bound of the range, provided that the upper bound is greaterthan the lower bound.

In some embodiments, the control circuitry can be configured to directthe electric field generating circuit to generate one or more appliedelectric field strengths selected from a range of between 0.25 V/cm to1000 V/cm. In some embodiments, the control circuitry can be configuredto direct the electric field generating circuit to generate one or moreapplied electric field strengths of greater than 3 V/cm. In someembodiments, the control circuitry can be configured to direct theelectric field generating circuit to generate one or more appliedelectric field strengths selected from a range of between 1 V/cm to 10V/cm. In some embodiments, the control circuitry can be configured todirect the electric field generating circuit to generate one or moreapplied electric field strengths selected from a range of between 3 V/cmto 5 V/cm.

In other embodiments, the control circuitry can be configured to directthe electric field generating circuit to generate one or more appliedelectric field strengths including 0.25 V/cm, 0.5 V/cm, 0.75 V/cm, 1.0V/cm, 2.0 V/cm, 3.0 V/cm, 5.0 V/cm, 6.0 V/cm, 7.0 V/cm, 8.0 V/cm, 9.0V/cm, 10.0 V/cm, 20.0 V/cm, 30.0 V/cm, 40.0 V/cm, 50.0 V/cm, 60.0 V/cm,70.0 V/cm, 80.0 V/cm, 90.0 V/cm, 100.0 V/cm, 125.0 V/cm, 150.0 V/cm,175.0 V/cm, 200.0 V/cm, 225.0 V/cm, 250.0 V/cm, 275.0 V/cm, 300.0 V/cm,325.0 V/cm, 350.0 V/cm, 375.0 V/cm, 400.0 V/cm, 425.0 V/cm, 450.0 V/cm,475.0 V/cm, 500.0 V/cm, 600.0 V/cm, 700.0 V/cm, 800.0 V/cm, 900.0 V/cm,1000.0 V/cm. It will be appreciated that the electric field generatingcircuit can generate an electric field having a field strength at atreatment site falling within a range, wherein any of the foregoingfield strengths can serve as the upper or lower bound of the range,provided that the upper bound is greater than the lower bound.

It should be noted that, as used in this specification and the appendedclaims, the singular forms “a,” “an,” and “the” include plural referentsunless the content clearly dictates otherwise. It should also be notedthat the term “or” is generally employed in its sense including “and/or”unless the content clearly dictates otherwise.

It should also be noted that, as used in this specification and theappended claims, the phrase “configured” describes a system, apparatus,or other structure that is constructed or configured to perform aparticular task or adopt a particular configuration. The phrase“configured” can be used interchangeably with other similar phrases suchas arranged and configured, constructed and arranged, constructed,manufactured and arranged, and the like.

All publications and patent applications in this specification areindicative of the level of ordinary skill in the art to which thisinvention pertains. All publications and patent applications are hereinincorporated by reference to the same extent as if each individualpublication or patent application was specifically and individuallyindicated by reference.

As used herein, the recitation of numerical ranges by endpoints shallinclude all numbers subsumed within that range (e.g., 2 to 8 includes2.1, 2.8, 5.3, 7, etc.).

The headings used herein are provided for consistency with suggestionsunder 37 CFR 1.77 or otherwise to provide organizational cues. Theseheadings shall not be viewed to limit or characterize the invention(s)set out in any claims that may issue from this disclosure. As anexample, although the headings refer to a “Field,” such claims shouldnot be limited by the language chosen under this heading to describe theso-called technical field. Further, a description of a technology in the“Background” is not an admission that technology is prior art to anyinvention(s) in this disclosure. Neither is the “Summary” to beconsidered as a characterization of the invention(s) set forth in issuedclaims.

The embodiments described herein are not intended to be exhaustive or tolimit the invention to the precise forms disclosed in the followingdetailed description. Rather, the embodiments are chosen and describedso that others skilled in the art can appreciate and understand theprinciples and practices. As such, aspects have been described withreference to various specific and preferred embodiments and techniques.However, it should be understood that many variations and modificationsmay be made while remaining within the spirit and scope herein.

1-15. (canceled)
 16. A medical device system comprising: an electricfield generating circuit configured to generate one or more electricfields; and a control circuit in communication with the electric fieldgenerating circuit, the control circuit configured to control deliveryof the one or more electric fields from the electric field generatingcircuit; two or more electrodes forming at least one electrode pair todeliver the electric fields to a site of a cancerous tumor within apatient; and wherein the control circuit causes the electric fieldgenerating circuit to generate one or more electric fields atfrequencies selected from a range of between 10 kHz to 1 MHz; whereinthe control circuit estimates a temperature of tissue within theelectric field based on an impedance measurement.
 17. The medical devicesystem of claim 16, wherein the control circuit estimates a temperatureof tissue within the electric field based on an impedance measurementand a distance between the electrodes of the electrode pair.
 18. Themedical device system of claim 17, wherein the medical device system isconfigured to receive data regarding the distance between the electrodesof the electrode pair.
 19. The medical device system of claim 16,wherein the control circuit estimates changes in temperature of tissuewithin the electric field based on changes in measured impedance. 20.The medical device system of claim 16, further comprising a heatingelement, wherein the control circuit causes the heating element togenerate heat.
 21. A medical device system comprising: an electric fieldgenerating circuit configured to generate one or more electric fields;and a control circuit in communication with the electric fieldgenerating circuit, the control circuit configured to control deliveryof the one or more electric fields from the electric field generatingcircuit; two or more electrodes to deliver the electric fields to a siteof a cancerous tumor within a patient; and an implantable temperaturesensor to measure the temperature of tissue at the site of the canceroustumor, the implantable temperature sensor in electronic communicationwith the control circuit; wherein the control circuit causes theelectric field generating circuit to generate one or more electricfields at frequencies selected from a range of between 10 kHz to 1 MHz.22. The medical device system of claim 21, wherein the implantabletemperature sensor is configured to observe thermal changes to tissueduring electric field generation.
 23. The medical device system of claim21, wherein the medical device is configured to turn off or stopgeneration of one or more electric fields if the temperature of thetissue exceeds a threshold.
 24. The medical device system of claim 21,further comprising a first lead providing electrical communicationbetween the control circuit and at least one electrode; wherein theimplantable temperature sensor is disposed on the first lead.
 25. Themedical device system of claim 24, the first lead comprising at leastone of a transcutaneous lead and a fully implantable lead.
 26. Themedical device system of claim 21, wherein at least two electrodes areconfigured to be implantable.
 27. The medical device system of claim 21,wherein the electric fields are delivered across at least one vectordefined by an electrode pair.
 28. The medical device system of claim 27,wherein the implantable temperature sensor is positioned between theelectrode pair.
 29. The medical device system of claim 21, wherein theimplantable temperature sensor is adapted to be inserted into thecancerous tumor.
 30. The medical device system of claim 21, wherein theelectric fields are delivered across at least two vectors, wherein afirst vector is defined by a first pair of electrodes and a secondvector is defined by a second pair of electrodes.
 31. The medical devicesystem of claim 30, wherein the electric fields along the at least twovectors are spatially and/or directionally separated from one another.32. The medical device system of claim 21, comprising at least twoelectric field generating circuits, wherein a first electric fieldgenerating circuit is implantable and a second electric field generatingcircuit is external.
 33. The medical device system of claim 21, furthercomprising an implantable housing, the implantable housing defining aninterior volume into which the electric field generating circuit and thecontrol circuit are disposed.
 34. The medical device system of claim 21,wherein the temperature sensor is selected from the group consisting ofa thermistor, a resistance thermometer, a thermocouple, and asemi-conductor based sensor.